The neurohypophysis is a neural extension of the brain, whose vasculature contains a unique system of portal vessels essential to the secretion of hormones. Physiological mechanisms regulating the neurohypophyseal vasculature have received little attention. The overall hypothesis of this project is that the neurohypophyseal vasculature being specialized in its function has developed specialized mechanisms of regulating tissue perfusion which differ both qualitatively and quantitatively from those found in other brain regions. We believe these mechanisms allow for a close coupling between neurosecretion and neurohypophyseal blood flow and that they are intrinsically mediated by local factors such as ions, peptides or autonomic nerves. For brain vessels, potassium mediation of cerebral vasodilation has been suggested as a mechanism of coordinating discharging neurons and adjacent cerebral vessels. Potassium is released from magnocellular neurons in the neurosecretory pro cess, but these effects have not been studied. We will determine whether neurohypophyseal blood flow correlates with the magnitude and timing of local potassium changes during neurosecretion. The influence of brain neurons on local blood vessels is controversial. Vessels in most areas of brain appear to be metabolically regula ted rather than primarily responsive to direct neuronal stimulation. Our previous work strongly suggests that central nervous system inputs account for neurohypophyseal vasodilation. We will study the effect of direct, neuronally released peptide, on the neurohypophyseal vasculature during conditions of physiologic vasodilation. The neurohypophysis receives anatomically significant peripheral autonomic inputs. We will test the hypothesis that these peripheral inputs are important to the regulation of neurohypophyseal vasodilation during well described physiologic stimulation by hypoxia and hypotension. The interrelationship of AVP neurosecretion and blood flow regulation will be described for all of the mechanisms investigated. This proposal will significantly increase our knowledge of factors regulating neurohypophyseal blood flow and improve our understanding of mechanisms that integrate neuronal activity with blood flow regulation. These data will aid our understanding of hormonal release and circulatory transport within the pituitary as both activities are finally dependent upon regional blood flow through neurohypophyseal tissue.